Anti-CCR9 Binding Molecules for Inflammatory Bowel Disease
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Solution Overview
Problem
Current therapies for inflammatory bowel disease (IBD) are inadequate, as they often fail to achieve durable remission in most patients and require surgical interventions in up to two-thirds of Crohn's disease patients over their lifetime.
Innovation Solution
Development of binding molecules that specifically target the chemokine receptor CCR9, inhibiting its interaction with CCL25, preventing CCR9 internalization, and inducing death of CCR9-expressing cells through antibody-dependent cell-mediated cytotoxicity (ADCC).
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies (aminosalicylates, corticosteroids, immunosuppressants) are used for IBD treatment, then symptomatic response is achieved, but durable remission is not achieved in the majority of patients
Solution Approach 1:
The patent extracts and targets the specific molecular mechanism (CCR9 receptor-CCL25 ligand interaction) that drives pathogenic cell migration to the gut. By isolating this specific pathway for therapeutic intervention using anti-CCR9 antibodies, the treatment achieves more reliable and durable remission by addressing the root cause of inflammation rather than providing broad-spectrum immunosuppression.
Solution Approach 2:
The invention changes the therapeutic parameter from non-specific immunosuppression to specific receptor-ligand interaction blockade. The anti-CCR9 antibodies modify the biological parameter of cell migration by preventing CCR9-expressing cells from responding to CCL25 chemokine signals, thereby reducing inflammatory cell infiltration into the gut and achieving sustained remission.
2Object-affected harmful factors
If step-up approach with multiple drugs is employed, then some symptomatic relief is obtained, but surgical intervention is required in up to two-thirds of Crohn's disease patients
Solution Approach 1:
The patent extracts the specific pathological mechanism (CCR9-mediated cell migration) from the complex inflammatory process and targets it directly. This focused approach eliminates the need for complex multi-drug regimens by addressing the key driver of disease progression through a single mechanism-specific antibody therapy.
Solution Approach 2:
Instead of using multiple drugs to suppress inflammation broadly, the invention inverts the approach by actively targeting and blocking the specific migration pathway that brings inflammatory cells to the gut. The anti-CCR9 antibody prevents pathogenic cell recruitment rather than suppressing the immune system globally, thereby reducing inflammation through a targeted mechanism.
3Strength
If CCL25 engagement is enhanced, then cell survival and resistance to apoptosis increase, but this promotes disease progression in IBD
Solution Approach 1:
The patent converts the harmful effect of enhanced cell survival (which normally protects pathogenic cells from apoptosis and promotes inflammation) into a beneficial therapeutic effect. By blocking CCR9-CCL25 interaction, the antibody prevents pathogenic cells from receiving survival signals, thereby inducing apoptosis of these harmful cells and reducing inflammatory persistence in the gut.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The binding molecules effectively inhibit the migration and survival of CCR9-expressing cells, potentially leading to improved treatment outcomes for IBD by reducing intestinal inflammation and promoting remission.
Implementation Method 1
binding molecules which bind to CCR9-expressing cells, inhibit the interaction between CCR9 and its natural ligand CCL25
Implementation Method 2
capable of inducing death of the CCR9-expressing cells to which they bind, for example by mediating an antibody dependent cell-mediated cytotoxicity (ADCC)
Implementation Method 3
inhibit the interaction between CCR9 and its natural ligand CCL25, preventing CCR9 internalization
Data Source
AI summary
The invention relates to binding molecules, such as antibodies, that bind to the chemokine receptor CCR9. More particularly, the invention relates to the treatment of CCR9-mediated diseases or conditions such as inflammatory bowel disease (IBD), and methods for the detection of CCR9, which make use of the binding molecules of the invention.